title: IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel α-L-iduronidase (IDUA) alleles.
abstract: Mutational analysis of the IDUA gene was performed in a cohort of 102 European patients with mucopolysaccharidosis type I. A total of 54 distinct mutant IDUA alleles were identified, 34 of which were novel including 12 missense mutations, 2 nonsense mutations, 12 splicing mutations, 5 micro-deletions, 1 micro-duplication 1 translational initiation site mutation, and 1 'no-stop' change (p.X654RextX62). Evidence for the pathological significance of all novel mutations identified was sought by means of a range of methodological approaches, including the assessment of evolutionary conservation, RT-PCR/in vitro splicing analysis, MutPred analysis and visual inspection of the 3D-model of the IDUA protein. Taken together, these data not only demonstrate the remarkable mutational heterogeneity characterizing type 1 mucopolysaccharidosis but also illustrate our increasing ability to make deductions pertaining to the genotype-phenotype relationship in disorders manifesting a high degree of allelic heterogeneity.
authors.affiliation: Consortium for Human Molecular Genetics, Milano Bicocca University, Monza, Italy. genemonza@unimib.it
authors.forename: Francesca
authors.initials: F
authors.lastname: Bertola
authors.forename: Mirella
authors.initials: M
authors.lastname: Filocamo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Casati
authors.forename: Matthew
authors.initials: M
authors.lastname: Mort
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymanska
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.forename: Orazio
authors.initials: O
authors.lastname: Gabrielli
authors.forename: Serena
authors.initials: S
authors.lastname: Grossi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Scarpa
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Parenti
authors.forename: Daniela
authors.initials: D
authors.lastname: Antuzzi
authors.forename: Jaime
authors.initials: J
authors.lastname: Dalmau
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi Vici
authors.forename: Ilyas
authors.initials: I
authors.lastname: Okur
authors.forename: Jordi
authors.initials: J
authors.lastname: Rosell
authors.forename: Attilio
authors.initials: A
authors.lastname: Rovelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Furlan
authors.forename: Miriam
authors.initials: M
authors.lastname: Rigoldi
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: David N
authors.initials: DN
authors.lastname: Cooper
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
mesh_terms: D000483:Alleles; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D004252:DNA Mutational Analysis; D005060:Europe; D005091:Exons; D056726:Genetic Association Studies; D006801:Humans; D007068:Iduronidase / Q000235:genetics*; D008969:Molecular Sequence Data; D008059:Mucopolysaccharidosis I / Q000235:genetics*; D020125:Mutation, Missense; D011487:Protein Conformation; D044465:White People / Q000235:genetics
chemical_list: D007068:Iduronidase